Human Optimization

SETTING YOUR HEALTH INTENTIONS FOR 2022

As we approach the end of another year, many of us are looking ahead to the New Year and setting resolutions or intentions for ourselves. One area that is ripe for change is our health. One great way to set healthy intentions for the New Year is by thinking about what you want to achieve physically, emotionally, and mentally. Maybe you want to lose weight, get in shape, or eat healthier. Perhaps you’d like to reduce stress levels or boost your energy. Here are some tips for setting effective health intentions for the New Year.

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WHY SETTING HEALTH GOALS IS IMPORTANT?

In medicine, we work daily with our patients and set goals we want them to achieve by their next follow-up visit. Setting these realistic goals allow for them to not only be an active participant in their health, but to create daily habits to achieve their optimal level of wellness. Similarly, you can set goals for yourself. Not only can setting health goals help you achieve your objectives, but they can also be a great source of motivation as well as encouragement as you work towards those goals on a daily basis.

HOW TO SET HEALTHY INTENTIONS?

First, you want to identify what it is that you want to change about your health.

Are you experiencing symptoms or do you want to prevent symptoms?

Are you feeling stressed out by the daily grind of life, are you not sleeping well at night, are you looking for an alternative way to manage symptoms of depression?

Do you feel like this is a good time in your life to achieve one of these objectives?

Once you have identified the things that you want to change, it is important to realize that change is a process and nothing will happen overnight. Remembering this can give you the motivation to push through those times when your progress is not as quick as you would like.

SUSTAINABLE, LONG-TERM GOALS

Once you’ve set realistic goals for your health, create small daily habits that can help you achieve your health objectives. For example, if your goal is to lose weight, schedule time each day for exercise and track your food intake. If sleep deprivation is affecting your mood or productivity at work, try to go to bed earlier or take a 20-minute nap during the day so you are more alert.

If you are struggling to stay motivated on your new behaviors, set up some accountability for yourself. For example, if you are trying to lose weight, tell a friend about your goals and ask him or her to check in with you daily on your progress.

Lastly, remember that achieving health goals is not only about the big picture of your overall well-being, but also the little things that we do each and every day. By committing to a health change and creating daily habits that can help you maintain this new behavior, you will be on your way to a happier and healthier 2022!

IMPORTANCE OF EATING HEALTHY & NOT FAD DIETS

Fad diets are common in the new year.  Many of these diets can help you lose weight quickly, but it is typically not sustainable and they provide no long-term benefits.

Eating healthy does not mean that you have to go on a strict diet or eat bland food. It simply means that the majority of your foods each day should be fresh fruits and vegetables, whole grains (e.g. brown rice or quinoa), lean proteins (e.g. fish, poultry, beans), and healthy fats (e.g. nuts, seeds, olive oil). While you can lose weight on these diets, they are not good for the body long-term since they do not include many of these important foods that contain antioxidants and other important nutrients that help us function optimally.

ARE YOU GETTING ENOUGH SLEEP?

Many times, when we don’t get enough sleep, we find ourselves reaching for a cup of coffee in the morning to wake up our brains and bodies. Or perhaps you have noticed that after a night without much sleep, your mood is less than stellar and you cannot concentrate as well at work.

While sleep is not the only factor in maintaining good moods or optimal energy levels, it plays an important role.  Make sure that you are getting 7-9 hours of sleep each night to maintain your health and wellness!

BRAIN HEALTH & EXERCISE – ALSO IMPORTANT FOR YOUR HEALTH

Studies indicate that participating in regular exercise helps prevent dementia, Alzheimer’s disease, and mild cognitive impairment. Regular exercise also has benefits for body weight, cardiovascular health, sleep quality, productivity at work, mood disorders (e.g., anxiety and depression), stress management, self-esteem and self-confidence, and the list goes on.

If you are not currently exercising regularly, start by committing to exercising 3-4 times per week for 30 minutes each time.  Remember to always speak with your physician before starting any exercise program!

It is also important to note that exercising does not have to be boring or strenuous. Find activities that you enjoy, such as walking, hiking, swimming, biking, yoga or dancing. And if you love a good workout in the gym, make sure you are getting results from all of your hard work!

BONUS: TIPS TO KEEPING YOUR HEALTH OPTIMIZATION GOALS ON TRACK 

– Map out your goal and the steps it will take to achieve this goal.  Be specific and realistic when you set your health optimization goals so that you can identify what is needed to reach your objective.

– Determine the resources available in order to meet these goals, such as time, money, family support, etc.

– Identify a support system of friends and family who are trying to achieve positive health changes as well. Having this network of people around you will help you stay accountable on your path to optimal health!

– Stay focused and dedicated to these new behaviors by reminding yourself why you made these goals in the first place.  Revisit your goal statement often, whether it is printed out and hanging near your computer or written on a notecard in your wallet. Having this daily reminder of why you are taking these steps to improve your health will help motivate you throughout the year and beyond!

– Track your progress and celebrate each success along the way. This does not mean that you need to weigh yourself every day, but rather take note of how you are feeling and how it is easier to stick with your new behaviors.

Health optimization is not an easy task, but by setting your intentions for 2022 now, you are preparing yourself to achieve these goals. So say goodbye to those FAD diets that promise quick weight loss or guilt-free eating habits that leave you feeling deprived. Instead, commit to making healthy lifestyle changes that will improve your health and wellness in the long term and make sure your friends and family are on board with keeping you accountable!

I hope that this article was helpful to you and wish you a very happy, healthy 2022.

Maryland Functional Medicine 

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DNA Methylation: What You Should Know

DNA methylation is a biological process that changes the structure of DNA. It can affect how tightly your genes are packaged and how easily they’re turned on or off. This process is an important part of normal cellular activity and helps protect cells from damage caused by stressors like toxins, poor diet, etc. Follow us on this week’s post to understand more about this process and its role in human health and longevity.

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WHAT IS DNA METHYLATION

Methylation is the addition of a methyl group (-CH3) to a molecule. In the context of DNA, it’s the addition of a methyl group to one of the bases, cytosine (C). DNA is formed by two strands that form a helical structure (also called the double helix). Each strand is comprised of nucleotide bases, which are labeled A, T, C, and G.[i] There are four types of DNA methylation:

1.  5-methylcytosine:  This is the most abundant and stable type of cytosine methylation.[ii]

2.  5-hydroxymethylcytosine: This is a byproduct of active DNA demethylation and can be reformed into cytosine methylation.

3. 6-methyladenine:  This is found in bacterial DNA and is a result of the methylation of adenine.

4. N6-methyladenine: This is also found in bacterial DNA and is the result of methylation of adenine, but it’s a result of a different enzyme system.

The addition of a methyl group to cytosine alters the way the DNA is packaged and can affect how genes are expressed. Methylated DNA is less accessible to proteins that read DNA ( transcription factors) and can lead to  gene silencing.

Silencing this process can change how genes are expressed. The methylated DNA is said to be “methylated” and the unmethylated DNA is said to be “unmethylated.” More than 70% of human CpG islands (sequences on chromosomes) are methylated.

DNA METHYLATION AND GENE EXPRESSION

When genes contain methyl groups, they tend to remain inactive and gene expression is decreased.  This is because methylation helps to “wrap” the DNA around proteins called histones, which keeps them from being accessed by transcription factors. Transcription factors refer to a group of proteins that bind to the DNA and help turn genes on or off.

Even though methylation can decrease gene activity, this process is important for normal cellular functioning. For example, it helps control inflammation by turning off genes that promote inflammation. It also helps turn off tumor suppressor genes in cells that don’t need to divide – like heart or nerve cells.

That being said, when it’s dysregulated, improper methylation has been linked with a variety of diseases, including cancer, Alzheimer’s disease, and autism.

The addition of a methyl group can also change the physical shape of the DNA molecule, making it harder for transcription factors to bind to it.

On the other hand, when genes are unmethylated, they tend to be turned on and gene expression is increased. When genes lack these methyl groups, the proteins they encode are more likely to be produced. This is why methylation can affect things like cancer development, as well as normal cell function.

HOW DOES DNA METHYLATION AFFECT THE BODY

DNA methylation is a necessary part of normal cellular function because it protects against stressors that can damage DNA. Cells are constantly under attack from harmful substances, radiation, toxins, poor diet, etc., so they have to be able to protect themselves. DNA methylation helps to do this by silencing genes that could cause damage.

When the body is healthy, DNA methylation works properly and everything runs smoothly. However, when the body is not healthy, it can lead to problems with methylation. For example, when a person is stressed out or has a poor diet, their cells become stressed and DNA methylation decreases.

PROBLEMS WITH DNA METHYLATION IN THE BODY

What causes improper methylation in the body?

There are a few things that can cause problems with methylation, including:

  • Nutritional deficiencies: A person who is deficient in certain vitamins and minerals (like B6, B12, zinc, and magnesium) may have problems with methylation.
  • Environmental toxins: Toxins from the environment can also interfere with methylation. These toxins include things like pesticides, herbicides, plastics, and heavy metals.
  • Inflammation: When the body is under chronic stress or has high levels of inflammation, it can have trouble with methylation. This is because high levels of free radicals can damage DNA and lead to problems with methylation. Methyl groups also help protect cells from free radical damage.
  • Age: As we get older, our ability to methylate decreases. This is because as we age, we lose cells that help with methylation, and our DNA becomes more susceptible to damage.[iii]
  • Genetics: Some people are born with genes that make it harder for them to methylate DNA properly.

DNA METHYLATION & LONGEVITY

While there is much to be discovered on DNA Methylation and longevity, there are some early indications that it may be involved in the aging process[iv]. One study showed that people with high levels of methylated DNA lived longer than those with low levels of methylated DNA. Another study showed that when cells are unable to methylate DNA, they age more quickly. More research is needed to determine the role of DNA methylation in longevity, but these early findings suggest that it may be important.

CONCLUSION

DNA methylation is a complex process that plays an important role in normal cellular function. When it’s properly methylated, it helps to protect against environmental stressors and inflammation. It also plays an essential role in mitochondrial function, which is important for energy production.

However, when the body becomes stressed – whether it’s because of deficiencies, toxins, inflammation, age, genetics, or other factors – then DNA methylation can become impaired.  This can lead to a variety of problems, including cancer, neurodegenerative diseases, and other health issues.  It’s important to understand how it affects you and what changes can be made for optimal health. We hope this article has helped shed some light on what DNA methylation is and how it works in your body. Follow us next week!

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

[i] https://www.genome.gov/genetics-glossary/Deoxyribonucleic-Acid

[ii] https://pubchem.ncbi.nlm.nih.gov/compound/5-Methylcytosine

[iii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482848/

[iv] https://pubmed.ncbi.nlm.nih.gov/16565708/

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OXIDATIVE STRESS: Deterioration of Our Cells

Oxidative stress is a term that refers to the deterioration of our cells and tissues due to an imbalance between the production of free radicals and antioxidants. Free radicals are highly reactive molecules with unpaired electrons, which can cause harm when they interact with other important molecules in our cells. Antioxidants, on the other hand, work by donating their extra electron to neutralize free radicals before they can do any damage. This balance between free radical production and antioxidant protection is essential for health because it has been shown that oxidative stress plays a role in many chronic diseases such as cancer, diabetes mellitus type 2, cardiovascular disease (CVD), Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), and more. There are many risk factors for oxidative stress including genetics, diet, exercise habits and environmental pollution. In this blog post we will be discussing what oxidative stress is, how it affects our body, and more!

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WHAT IS OXIDATIVE STRESS?

Oxidative stress is a natural phenomenon that occurs through metabolic processes in the body. It’s made by the release of free radicals during the process of lipid peroxidation, which involves an enzyme called lipoxygenase producing ROS while breaking down fats under oxidative conditions.[i] In other words, oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the body’s ability to protect itself with antioxidants. Reactive oxygen species refers to oxygen molecules that have unpaired electrons, making them “reactive”. ROS is made when oxygen interacts with other compounds; this can be caused by many external factors such as air pollution or cigarette smoke. When the produced ROS exceeds the body’s protection (antioxidants), it causes the oxidation of important molecules like DNA, proteins, and lipids (fats). These ROS include free radicals such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, which form during normal metabolic processes. Superoxide anions refer to the combination of two oxygen molecules to form a free radical. This compound lacks an electron and can damage different types of biomolecules such as DNA, proteins, and lipids through oxidation. Hydrogen peroxide is made when superoxide anions break apart and are known as the primary toxic molecule of ROS. Hydrogen peroxide can also damage DNA, proteins, and lipids by oxidizing them. The hydroxyl radical is formed when hydrogen peroxide reacts with the superoxide ion, producing highly reactive OH-radicals that break down cell membranes and tissues in the body.

The release of these free radicals increases when there is damage to mitochondria in our cells, which is crucial for producing energy. Mitochondria (the part of our cells that turns food into energy) has to work harder during oxidative stress and requires large amounts of antioxidants.[ii]

HOW DOES OXIDATIVE STRESS AFFECT OUR BODY?

Because oxidative stress involves the production of free radicals, it can damage many types of molecules in our cells such as lipids (fats) and DNA. This is important because cell membranes and DNA are largely made up of lipids and contain genetic information that tells our body how to function. A study found that when there is an imbalance between ROS and antioxidants, it can cause oxidative damage to lipids in our cells. This is important because lipids are the fatty molecules that form cell membranes and protect our cells from foreign objects. When lipid peroxidation occurs, free radicals attack the lipids in cell membranes damaging them. When the cell membrane becomes damaged, it increases permeability which allows molecules to leak into the cell causing further damage to proteins and other important molecules. Free radicals can also directly cause oxidative stress through DNA damage. [iii]This occurs when free radicals combine with oxygen in essential parts of our DNA such as the mitochondrial genome, which is crucial for producing energy within cells. The combination of these oxidative damages creates a domino effect throughout our body cells. Damage to DNA results in the inability of cells to divide properly, which leads to uncontrolled cell growth. This can cause tumors and cancerous tumor cells to form all over our bodies. Damages caused by oxidative stress on lipids (fats) is important because fats are part of the lipid bilayer that forms the outer membrane of every living cell. When the lipid bilayer is damaged by ROS it leads to improper functioning in cells throughout our body.

When our body is under oxidative stress, there’s an accumulation of free radicals in our cells which results in damages to molecules like lipids (fats) and DNA. This can cause many problems in different parts of the body including:

– Increased atherosclerosis, is where plaque build-ups form in arteries causing them to harden.

– Increased risk for developing cancer and tumors because of DNA damage caused by ROS.

– Damages to cell membranes that lead to improper functioning in cells throughout our body.

COMMON SOURCES OF OXIDATIVE STRESS

Oxidative stress can be caused by many factors including environmental pollutants such as cigarette smoke, ultraviolet (UV) radiation from the Sun, and chronic infections like hepatitis. There are several other common sources of oxidative stress including:

– Smoking tobacco

– Eating high-calorie meals that contain a lot of fat, which can lead to obesity and increase the risk for cardiovascular disease.

– Consuming caffeine or alcohol in excess, because these substances inhibit enzymes that produce antioxidants in our body.

– Consuming a poor diet which may lack the necessary vitamins and minerals needed to make antioxidants in our body.

– Living a sedentary lifestyle, because can lead to weight gain that results in cardiovascular disease.

– Exposure to pollutants, which can come from the workplace or even the local environment.

One of the biggest sources of oxidative stress is exposure to sunlight. [iv]UV radiation that comes from sunlight has many harmful effects on our body including skin cancer because it promotes free radical formation in our bodies. When we are exposed to UV radiation it causes oxidation reactions in the skin, which damage proteins like collagen. Collagen is what gives our skin its strength and elasticity. When it becomes damaged, these effects lead to wrinkles and sagging in our skin.

Oxidative stress is a term that refers to the deterioration of our cells and tissues due to an imbalance between the production of free radicals and antioxidants. But what does this have to do with longevity?  Studies show that people who experience high levels of oxidative stress during their lifetimes may be at greater risk for developing dementia or other age-related diseases later on in life. There are many ways in which we can help reduce oxidative stress, such as with antioxidant rich foods. What are some easy ways you have increased your antioxidant intake lately? Share with us in the comments below or follow us on next week’s blog for more information related to oxidative stress and longevity.

[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/#:~:text=Oxidative%20stress%20is%20a%20phenomenon,to%20detoxify%20these%20reactive%20products.

[ii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145906/#:~:text=Oxidative%20stress%20is%20characterized%20by,homeostasis%20and%20mitochondrial%20defense%20systems.

[iii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC484183/

[iv] https://pubmed.ncbi.nlm.nih.gov/29124687/#:~:text=The%20generation%20of%20reactive%20oxygen,mechanisms%2C%20oxidative%20stress%20can%20develop.

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

Maryland Functional Medicine 

Maryland Functional Physician

Maryland Functional Doctor

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WHAT IS MITOPHAGY?

Mitophagy is a process that occurs in cells, and it’s essentially the destruction of old or dysfunctional mitochondria. It’s important to know about mitophagy because as we age, our bodies lose their ability to carry out this process properly. When mitophagy does not occur properly it can lead to mitochondrial disease which has been linked to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. This blog post will provide an overview of what mitophagy is and why it matters.

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WHAT IS MITOPHAGY

The word ‘mitophagy’ was coined in 2007 by the researchers who discovered this process. The prefix mit- means thread and phage means eat, so we define mitophagy as the destruction of mitochondria via a cellular mechanism called autophagy. Autophagy is a process that involves the degradation and recycling of cellular components. Mitophagy is the selective kind of autophagy mechanism that removes mitochondria.  A cell can digest its own organelles through this process, but it will only remove damaged structures and not healthy structures. This selective quality is what makes mitophagy so unique because most other forms of autophagy just degrade cellular components indiscriminately.

There are two other forms of autophagy: chaperone-mediated autophagy and micropexophagy. [i]

  1. Chaperone-mediated autophagy is a process that degrades damaged proteins and this type of degradation occurs in the lysosome or sac like structure.
  2. Micropexophagy on the other hand targets  mitochondria for degradation.

MITOPHAGY & MITOCHONDRIA

The mitochondria is an organelle that is responsible for converting energy into a form of molecules that our cells can use.[ii] Inside the mitochondria are enzymes called electron transport chains (ETCs) which take electrons and try to pair them with hydrogen atoms to produce chemical energy. This process also creates free radicals as by products, so our cells must have an enzyme called superoxide. Superoxide dismutase (SOD) eliminates superoxides and turns them into hydrogen peroxide. Hydrogen peroxide (H2O2) is broken down by catalase and glutathione peroxidase into water and oxygen gas.

This cellular structure is responsible for helping generate ATP (Adenosine triphosphate) which stores energy in the form of phosphate bonds. Cells need ATP to get rid of excess calcium ions that build up due to metabolism, and also to open up calcium ion channels for muscle contraction. Severing of the mitochondria from the rest of a cell triggers apoptosis, which is a programmed form of cellular death. The lack of a link to other organelles and its proximity to calcium ions makes it susceptible to damage. Because of this susceptibility, cells have developed a mechanism which allows them to dispose of defective mitochondria.

HOW DOES MITOPHAGY WORK

Mitophagy is a type of autophagy and there are three steps that must occur for this mechanism to carry out successfully:[iii]

1. The first step is the creation of an isolation membrane which surrounds the mitochondria, so the rest of the cellular components aren’t degraded.

2. The isolation membrane which elicits the form of selective degradation known as mitophagy is created by a multi-protein complex called PINK1 and Parkin.

3. The last step involves the elimination of the mitochondrion through fusion with lysosomes (the cellular structure responsible for degrading other organelles) via a double membrane structure called an autophagosome.

TYPES OF MITOPHAGY

There are two types of mitophagy that exist: Macro-autophagy and Micro-autophagy.

Macroautophagy begins with the formation of an isolation membrane around the mitochondria from a multi-protein complex composed of several proteins such as Nix, Parkin, AIFm2 and FUNDC1.

This isolation membrane then fuses with a lysosome which creates an autophagosome. The autophagosomes carry the mitochondria to the cytoplasm for degradation into amino acids, fatty acids, and nucleotides.

Microautophagy is a process that creates a small isolation membrane around the mitochondria from a single protein called Ulk1. This process is often used in response to stress, but there hasn’t been direct evidence of this process occurring in mammalian cells.

HOW IS MITOPHAGY REGULATED?

A protein complex called PINK1-Parkin is believed to be the primary regulator of mitophagy.  This complex is required for creating the isolation membrane that leads to mitophagy.

PINK1 has been found to regulate this process by promoting mitochondrial fission, imparting an isolation membrane around the mitochondria, and recruiting Parkin which becomes phosphorylated in response. When PINK1 is degraded or loses function through mutations, it can lead to PINK1-associated Parkinson’s disease.

Parkin is also required for mitophagy, and it acts in a parallel pathway to that of the PINK1-Parkin complex by creating an isolation membrane around mitochondria through phosphorylation of proteins involved in fission which leads to the formation of an autophagosome.

This suggests that PINK1-Parkin play a major role in the regulation of mitophagy.

MITOPHAGY IN DISEASE

Mitophagy is often found to be defective in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease[iv]. This is because faulty mitochondria are not properly eliminated, leading to cellular damage.

Since mitophagy is important in neuronal function, it follows that this process would be affected in cancer disorders. Cancer cells often have uncontrolled mitochondrial biogenesis, and this leads to extreme energy demands in cancerous cells which can be exploited. Mitochondrial biogenesis refers to the creation of new mitochondria from the division of existing ones.[v] This process is regulated by a protein complex that includes PGC1α and NRF1, which are often over-activated in tumor cells.

Cancer cells also need the ability to oxygenate themselves, so putting selective pressure on these cells through drugs that inhibit mitochondrial function can lead to their death. Inhibiting mitophagy could potentially decrease the effectiveness of such chemotherapy treatments, however research has shown that some chemotherapy drugs stimulate mitophagy so it may still have some use.

In addition, mitophagy is important for cardiovascular function and the development of stem cells. Mitochondrial biogenesis is a crucial process for stem cell formation and differentiation into progenitor cells. Mitophagy also ensures that damaged mitochondria are eliminated in cardiovascular cells.

Mitophagy is important to our longevity and healthspan because it allows the removal of faulty mitochondria that could potentially lead to cell death. Cell death leads to the death of the organism, so this process is critical for cellular health. Maintaining optimal cellular health is a key component in healthy aging, and efficient mitophagy is necessary for elimination of damaged mitochondria. We would love to see you next week on another blog post – Tune in then!

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900761/

[ii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630798/

[iii]

[iv] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017092/

[v] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883043/

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FISETIN: Why are people taking this supplement?

Fisetin is a flavonoid found in many fruits and vegetables. It has been shown to have anti-inflammatory, antioxidant, and anticancer effects. Because of the potential health benefits it may provide, fisetin supplements are becoming more popular as people look for alternatives to other medications that they may not be comfortable with or want to take long term.  In this blog post we will explore what fisetin is, why people are taking it, potential benefits and discuss current research being done around Fisetin and how this could impact future treatments available for those looking to improve their health naturally.

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Origins & History of Fisetin

Fisetin is a naturally occurring flavonoid compound. Flavanoids are water-soluble compounds found in plants and have antioxidant properties. Water-soluble means that Fisetin can dissolve in water. Fisetin is not found to be fat-soluble, which means it cannot dissolve into fats or lipids that are normally soluble in oils. Fisetin was isolated from the Fruiting bodies of a Fungus called Fomes Fomentarius. The Fruiting body of this fungus is responsible for producing all of the spores that are used to reproduce. Fisetin can also be found in many plants including Ginko Biloba, strawberries, persimmons. Fisetin’s chemical structure was first identified chemical formula was first described by Austrian chemist Josef Herzig in 1891. Fisetin can be found throughout the plant kingdom, where it acts as a photosynthesis inhibitor and UV protectant. Fisetin has even been isolated from insects, including ants, aphids, and wasps.

Fisetin is also said to be one of the many flavonoids that are found abundantly in the plant subfamily Cornoideae, which includes Foeniculum vulgare, Foeniculum dulce, and Coriandrum sativum. Fisetin was first isolated from Foeniculum vulgare, Fennel. Fisetin was first isolated from the bark of the Pacific wax myrtle tree and has since been found in many fruits and vegetables. Fruits and vegetables that are high in fisetin include:

– Strawberries; specifically, they are Fisetin’s highest food source.

– Red grapes

– Apples

– Asian pear

– Fennel seeds  (Foeniculum vulgare) Fisetin is a member of the flavonoids, which are plant pigments produced by many plants to help protect themselves from outside stressors, such as ultraviolet light, insects, and herbivores.

Why are people taking Fisetin?

Natural supplements are becoming increasingly popular in the health and wellness community. There are a number of different types of natural supplements such as probiotics, prebiotics, digestive enzymes, amino acids and herbal extracts that all serve their own specific purposes. There are many reasons why people take natural supplements. Some people want to support their bodies’ natural processes, others want natural help with a specific health concern, and some just want to maintain good health. Dietary supplements have been one way that consumers have sought to fulfill unmet dietary needs. Fisetin is one of many supplements like this that people are turning to attempt to make themselves feel better. Many of my patients opt to take supplements to make sure they get enough essential nutrients and to maintain or improve their health.

POTENTIAL BENEFITS

Fisetin is a naturally occurring antioxidant found in many fruits and vegetables. Fisetin is known as a neuroprotective agent, meaning it has been shown to have potential benefits in helping the body fight against both acute and chronic neurological diseases.  Fisetin is one of the most common and bioactive flavonoids which possesses potential neuroprotective effects. Fisetin also enhances learning and memory, decreases neuronal cell death, and suppresses oxidative stress.  Fisetin has been shown to have significant protective effects on the body from oxidative stress, which is why Fisetin may be taking it as it can potentially be beneficial for those looking to improve their health or prevent disease. Oxidative stress refers to the level of damage done to cells in the body by free radicals. Fisetin has been shown to have some effect against oxidative stress, but it is not yet known whether Fisetin itself can actually reduce oxidative stress or if Fisetin can enhance antioxidants that are already present in the body. It is also unknown how Fisetin works as an antioxidant. Fisetin may work as a scavenger, Fisetin can bind to free radicals, Fisetin could be regenerating the antioxidants that it is acting with, or Fisetin itself may act as an antioxidant. There is still much to learn about Fisetin.

FISETIN AND LONGEVITY

As we age, we accumulate damaged cells. Damaged cells can cause tissues to function improperly or not work at all. Fisetin has been shown to reduce senescent cell burden in mice by activating the body’s enzymes that clear out senescent cells. Senescent cells are cells that have stopped dividing to replicate themselves. Senescent cells can accumulate in all tissues with age and secrete pro-inflammatory cytokines and chemokines. Fisetin has been shown to increase the lifespan of mice. In a recent study, Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.

FISETIN & and mTOR

mTOR is responsible for controlling cell growth, division, and metabolism. Recent research shows how Fisetin inhibits the mTOR pathway. When you inhibit the mTOR pathway you are essentially slowing down the aging process.

Fisetin & Inflammaging

Inflammaging refers to the chronic low-grade inflammation that is caused by cellular damage, oxidative stress, and mitochondrial dysfunction. Fisetin is believed to be able to reduce inflammation because Fisetin has shown an ability to reduce cellular (nuclear) damage in animal studies. This is accomplished by Fisetin’s ability to inhibit by inhibiting pro-inflammatory enzymes and substances, like lipoxygenases and NF-kB.

FUTURE RESEARCH

As research continues on this compound more information about how fisetin could be used for medicinal purposes will be revealed. Fisetin holds great potential for multiple applications in medicine, and research studies have shown Fisetin’s positive anti-inflammatory and anticancer effects on different cell types. Over the last two decades, much attention has been drawn to plant-derived bioactive compounds as novel therapeutic agents for treatment of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The current research suggests that the benefits of Fisetin may be worth considering for those looking for natural options to improve their health.

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

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EXTRACELLULAR MATRIX

The extracellular matrix is a network of proteins and other molecules in the space between cells. It helps cells attach to one another and move around. You can think about this like scaffolding for building a house: it provides support and structure for all kinds of activities inside the cell without getting too involved in how those things happen. When there’s damage or injury, it also sends signals to help repair or replace damaged parts of tissue by recruiting stem cells from elsewhere in the body. In this blog post, we will explore how extracellular matrix regulation works to maintain homeostasis from birth to death so you can better understand your body’s natural aging process!

WHAT IS THE EXTRACELLULAR MATRIX?

The extracellular matrix (ECM) is a dynamic structure that provides a structural framework for cellular organization and movement. It is a three-dimensional space, extending between cells that are defined by components produced by the cells themselves as well as cells that they neighbor.

The ECM consists of a dynamic mixture of structural proteins which are typically secreted from the cell into the extracellular environment. The extracellular matrix is made up of many components, including molecules like collagen and elastin, macromolecules like glycoproteins or proteoglycans, proteins like adhesion proteins that allow cells to bind to each other, growth factors that signal new tissue formation, and others.

Collagen is one of the most prominent components of the extracellular matrix. It provides strength and stability to tissues and is primarily responsible for wound healing and tissue repair.

There are many types of glycoproteins, or proteoglycans, which give the matrix its winding appearance, similar to DNA’s iconic double helix. These macromolecules allow cells to recognize and bind to the matrix components.

Several types of adhesive proteins promote cell-to-cell contact, which can be found on either side of a plasma membrane where they’ll spread out from the cell’s surface towards the extracellular matrix. These proteins will crosslink, or bond together with other adhesive proteins to form a mesh that reinforces the adhesive bond between cells.

4 Major Purposes of the Extracellular Matrix:

Containment of cell growth: This refers to how the matrix can “wrap” around cells while still allowing them to grow in size while confined by the surrounding ECM.

Cell signaling and communication: Cell signaling and communication refer to how cells can send signals through the matrix so that growth and development happen in the right place at the right time.

Binding cells together to form tissues or organs:  The adhesion proteins that hold cells together can also link them to the extracellular matrix.

Removal of dead or damaged cells from the body:  Cells are constantly dying and being replaced, so the ECM will send signals to attract stem cells that can migrate towards their location within tissue in order to repair or replace damaged cells.

HOW DOES THE EXTRACELLULAR MATRIX REGULATE CELL BEHAVIOR?

The extracellular matrix is a critical mediator of cell behavior. In fact, cells respond to their environment by changing shape and altering gene expression in order to perform their job properly. 

Cell adhesion: This refers to how cells bind together very tightly with adhesive proteins that can crosslink with other adhesive proteins across the plasma membrane so they strengthen the bond between cells.

In order for cells to join together correctly at the right times and places, they need to be able to sense their environment and respond by sending signals through a network of proteins that bind together in a very specific way. So if a developing embryo is going to form into multiple layers that will eventually become distinct tissues or organs, cells in each layer will need to bind to the ECM and pass signals through it to be able to change shape and function into whatever they’re supposed to become.

3 Types of Cell Adhesion:

Integrin: These proteins anchor cells to the extracellular matrix, primarily binding between adhesive proteins on one side of a plasma membrane and “integrin-binding sites” on the other side of the plasma membrane.

Cell-matrix adhesion: This refers to how cells can bind directly to ECM components, which involves integrins as well as other types of adhesion proteins.

Compartmentalization/Segregation: This refers to how cells can create closed boundaries that will separate different tissues from each other.

In order for cells to be able to create compartments, they need to regulate the way substances enter and exit the local environment. In fact, many types of tissue have a limited list of molecules that can diffuse across their borders in one direction or another – this is called “selective permeability”, and it’s a feature of many cell types.

2 Main Features of Selective Permeability:

1) Pores in the plasma membrane allow solutes to move through them but prevent water from moving freely through those pores, due to the presence of lipid bilayers. This allows cells to selectively control which molecules can enter or exit their local environment.

2) Cells can have a different level of permeability in different directions, so some proteins will move freely across the cell membrane while others cannot – this is called “anisotropy”.

HOW DOES SELECTIVE PERMEABILITY WORK?

Different types of cells can adjust how permeable their plasma membranes are to help create local boundaries and also take in the right molecular nutrients for their job. In regards to the extracellular matrix, the ECM can bind to integrins on the plasma membrane of cells, which helps create a boundary that separates tissues from each other. Integrins are the major cell adhesion proteins, which means they bind cells to the ECM. Cells will be able to pass molecules through the border into neighboring tissues, but if the molecule is too large it won’t fit through the pores of the membranes and therefore cannot go across. All cells have distinct levels of permeability in different directions to help create a very specific environment for each cell type.

EXTRACELLULAR MATRIX & LONGEVITY

Part of what allows cells to remain differentiated is the extracellular matrix. It provides cells with the appropriate molecular signals to maintain their state, and when they move to a different tissue it also helps ensure that they will behave correctly in their new local environment – which is why this system breaks down when there is damage or disease. Abnormalities in the extracellular matrix are linked with age-related diseases. When ECM is broken down, it releases many different molecules that can cause inflammation. Inflammation is an immune response meant to eliminate threats to the body, but chronic inflammation can be very harmful and eventually result in death. When this happens over time the extracellular matrix will degrade and build up in ways that are detrimental to our health. When this happens, it causes “inflamm-aging” which is when inflammation builds up over time due to wear and tear on the body.

As we age, the extracellular matrix continues to degrade in many ways. The aging process involves many deleterious changes in the cells and tissues of an organism, which can affect how it functions. Lifestyle factors may accelerate the degradation of the extracellular matrix. Since ECM is responsible for cellular differentiation, preventing this degradation could lead to greater longevity because it would allow cells to maintain their state and continue functioning properly.  

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

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CELL DANGER RESPONSE: What it is and why its important

The body’s immune system is a complicated, elegant machine that protects us from the outside world. It does this by recognizing invaders through amazing sensing mechanisms and responding to them with incredible precision. In the case of cell danger response (CDR), our cells do their best to protect themselves as they are being attacked by viruses or bacteria. Yet CDR can be dangerous if it overreacts and causes inflammation – which can lead to chronic diseases such as diabetes or even cancer. In this week’s blog post we will not only explain what CDR is but also how we minimize its risks so we may live a healthy life.

WHAT IS THE CELL DANGER RESPONSE?

The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. 

How it works is by the cell senses that it is being attacked, then using specialized proteins to monitor our metabolism. When CDR is activated, the body will use available energy sources and switch its focus to self-defense rather than growth and reproduction. CDR is a mechanism that allows cells to sense ‘danger’ that may be caused by viruses or bacteria. This danger can also come in the form of molecules such as DNA, RNA, and proteins – all of which are components found inside our cells.  When these substances get leaked into the extracellular environment, CDR kicks into gear.

The activated CDR will then enter into a cascade – this is where it gets its name, the danger response cascade (DRC). The danger response cascade can be broken up into five steps that occur in succession: 

1. Detection: Detection of PAMPs (e.g., pathogen-associated molecular patterns like lipopolysaccharides) or damage-associated molecular patterns (DAMPs). PAMPs are substances that can be recognized by specialized receptors, such as Toll-like receptor (TLR), NOD-like receptor (NLR), and RIG-I like helicases (RLH). DAMPs refer to the cellular debris or damage that results from being attacked. 

2. Activation of MAPKs, IKKɛ, TBK1, PKA, and PKR. Next these activated enzymes activate transcription factors (which refers to a biochemical process by which a particular gene’s instructions are copied into RNA) that then activate or suppress inflammation-promoting genes while suppressing other essential genes involved in repair pathways. When we discuss activated enzymes, this refers to enzymes that have been phosphorylated, which means a phosphate group has been added to the enzyme.  

3. Activation of transcription factors such as NF-kB, FOXO3a, and HIF1α. These transcription factors then go on to stimulate or suppress the transcription of genes that regulate inflammation and also cell survival. 

4. Activation of MDA5 & RIG-I: MDA5 and RIG-I are critical to the CDR response because they activate an antiviral pathway known as type I interferon production. Type I interferon production is a pathway that allows our body’s immune system to help fight infections. 

5. Secretion of inflammatory cytokines to induce downstream immune cells to take action against the infection. Inflammatory cytokines are a group of signaling proteins that trigger inflammation at sites of infection. The cells which release these cytokines are called antigen-presenting cells (APCs) and include monocytes, macrophages, dendritic cells, and B lymphocytes. This cascade is what allows CDR to induce inflammation – yet it can have negative consequences if activated over and over again.

In addition, CDR can also occur in response to non-infectious stresses such as heat, UV irradiation, and oxidative stress. These stresses have been shown to activate IKKɛ (which is one of the last components in the cascade) and cause it to activate NF-κB (Nuclear factor-kappa B). When activated, this protein moves into the nucleus where it works with other transcription factors to promote the expression of genes that trigger inflammation. It is important to note that these events happen within minutes of your body detecting CDR triggers. 

WHAT IS THE DANGER RESPONSE CAUSED IN THE BODY?

Inflammation is a vital part of the CDR cascade. It’s what helps cells fight off disease, but there are consequences if it goes on for too long or isn’t properly regulated.  Left unchecked, inflammation can lead to several chronic conditions. 

 Inflammation has been linked to cardiovascular disease, arthritis, atherosclerosis, type 2 diabetes, Alzheimer’s disease, and even depression. One of the most well-known links between inflammation and chronic illness comes from the research of Dr. Robert Ader. In 1974 he conducted a study in which two groups were given an antitoxin to protect against poison. 

 Group A only received the treatment, while group B also had their spleens removed beforehand to prevent their immune systems from mounting an inflammatory response. After receiving the antitoxin both groups were then injected with the poison. However, unbeknownst to them this second injection was not actually poisonous but just saline solution therefore they should not have gotten sick. 

To the surprise of the researchers, group B got just as sick as group A even though they did not have an immune system. Basically, because their bodies had already mounted an inflammatory response when injected with the saline solution it was interpreted by their brains to be a poison so they could become ill. This example is just one of many that illustrate how chronic inflammation can lead to the development of disease.

HOW CAN WE AVOID THE DANGER RESPONSE?

The answer to this question is multifactorial. First, it’s important to avoid or control infections with your immune system because that is what triggers the response in the first place.  

Second, it’s also best to take care of your body. This means eating a healthy diet, exercising regularly, practicing stress management, and more. 

Third, optimizing your immune system is important.  The better it functions the less likely you are to succumb to disease and the more effective it will be at fighting off infections.

Fourth, protect your cells from damage and stress by limiting exposure to toxins and sources of oxidative stress such as UV radiation and environmental pollutants. This includes using antioxidants that can directly neutralize free radicals before they do damage: vitamin C, vitamin E, manganese, selenium, copper, zinc, and more.

Finally, genetic variation also determines how many times your immune system can mount a CDR response before producing dysfunctional cells. This means that although the danger responses in everyone are the same there is a big difference in their potential scope because of individual genetics. Different SNPs have also been linked to an impaired danger response.

Although the danger response is an important part of fighting infections, it can also be responsible for chronic inflammation which has been linked to many health problems. Fortunately, there are things you can do to prevent this from happening. By implementing lifestyle changes you can help your body fight off disease while simultaneously protecting your cells from damage. 

How can the Institute for Human Optimization help you? At IfHO, we utilize a personalized, precision-based approach to medicine. Precision Medicine acknowledges individual differences in genes.  By having a better understanding of the individual’s genes and making therapeutic decisions based on their genetics, we can work together to drive CDR in a desirable direction.   

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

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METABOLIC ENDOTOXEMIA

Metabolic endotoxemia is a condition that affects many people in America. In fact, recent studies estimate that over one-third of adults in the United States have this health issue. It’s been estimated that it may soon be indirectly a leading cause of death. Follow us on this week’s blog to learn what it is and how to prevent metabolic endotoxemia.

Metabolic Endotoxemia

Metabolic endotoxemia is the presence of too much LPS (lipopolysaccharides) in the blood. LPS are toxins that reside on the outer membrane of bacteria that would otherwise not be allowed into our bloodstream. The American Diabetes Association identified bacterial lipopolysaccharide (LPS) as the inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes.  LPS triggers a cascade of immune responses. For example, after binding to its receptor TLR4 (TLR4 is a receptor found on the surface of cells that can detect LPS) or CD 14, there is an elevated level of tumor necrosis factor-alpha (TNFα). TNFα is a protein signaling molecule that is an inflammatory mediator that triggers the innate immune response. The innate immune system, as its name implies, is a primitive type of immunity that all living organisms have. In contrast to the adaptive immune system (which is found in humans and other higher-order species), there are no actual distinguishing features between cells belonging to the innate system or adaptive immune system – they simply look different. TNFα activates more TLR4 which results in more TNFα. As you can see, it becomes a vicious cycle leading to chronic inflammation.

LPS also induces cytokine production by activating inflammatory transcription factors known as nuclear factor kappa B (NF-κB). NF-κB is a protein complex that controls the expression of genes involved in immunity and inflammation. Inducing cytokine production helps our bodies fight off infections. However, it also activates the immune response to clear away cells that are injured or damaged by short-term inflammation. If this clearing of dead cells occurs chronically, it can lead to tissue damage and autoimmune diseases where the body starts attacking its own healthy tissues.

DIET & METABOLIC ENDOTOXEMIA

Paracelsus, a Renaissance physician said: “All things are poison; everything is poisonous; there is nothing without poisonous qualities. Only the dose permits something not to be poisonous.” 

The severity of this disorder depends on how much LPS enters circulation and how sensitive an individual’s body is to these inflammatory agents. As expected, diet and lifestyle are critical when it comes to metabolic endotoxemia and other diseases. 

Inflammatory transcription factors are also activated in response to a high-fat diet rich in saturated fats and low in fruits and vegetables. Inflammatory transcription factors are transcription factors that contribute to the initiation, regulation, and mediation of inflammation.

Saturated fatty acids trigger macrophages to create a cascade of inflammatory signals. Saturated fats refer to a type of dietary fat with no double bonds between the carbon atoms. They are typically solid at room temperature and found in foods such as beef, pork, poultry, butterfat (in dairy products), palm kernel oil, lard (in meat products), and cocoa butter. Inflammatory foods have been linked to causing an inflammatory immune response that results in endotoxemia, which is the presence of bacterial endotoxin (LPS) in the bloodstream.

METABOLIC ENDOTOXEMIA AND DISEASE

The relationship between metabolic endotoxemia and the onset of diabetes, obesity, and heart disease is well established. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. In a healthy body, insulin resistance may be caused by high cortisol levels in response to stress. This insulin resistance is typically temporary as a protective mechanism for the body, but in most people who are insulin resistant, a high carbohydrate diet makes them even more insulin resistant. So, these individuals will typically crave carbohydrates when their blood sugar is low from the stress cortisol is causing on their bodies with elevated insulin resistance.

Metabolic endotoxemia causes an increase in persistent free radicals, which contributes to chronic inflammation and aging of the cells. An increase in persistent free radicals is not optimal as this can result in the accelerated development of chronic disease. Chronic inflammation is cause for concern because it is associated with elevated risks of cardiovascular disease, Alzheimer’s disease, cancer, and many other chronic diseases. Metabolic endotoxemia also causes oxidative stress. Oxidative stress refers to the process whereby free radicals in cells cause damage to molecules leading to tissue and organ dysfunction. The human body has both antioxidant and anti-inflammatory mechanisms in place that operate in a feedback loop, such as red blood cells, white blood cells, vitamins C and E, uric acid, nitric oxide synthase (NOS), and more. This feedback loop works by protecting the cells from oxidative damage and removing damaged cells. However, there are many variables that can break the loop using mechanisms called hormesis. Hormesis refers to acute stress that leads to a beneficial effect. For example, exercise causes the body to emit oxidizing free radicals because it requires large amounts of ATP (energy) for muscle contraction. Metabolic endotoxemia however is not a beneficial mechanism. It is the result of an overload of free fatty acids (FFAs), cytokines, and NOS-derived NO which cause circulating endotoxins to disrupt the host’s metabolism. 

Additionally, oxidative stress decreases cellular DNA repair. Cellular DNA repair is critical to our overall health and well-being. As we have discussed in recent blogs, DNA repair is critical for maintaining metabolic homeostasis. Failure to maintain metabolic homeostasis due to DNA damage from oxidative stress can lead to obesity, insulin resistance, and even type 2 diabetes.

In addition to causing insulin resistance and oxidative stress, metabolic endotoxemia has been linked to dysfunction of the hypothalamic-pituitary-adrenal axis. Our HPA Axis is critical for maintaining metabolic homeostasis. Our HPA Axis is responsible for the release of cortisol, our main stress hormone. We often think of the HPA Axis as being involved in stress but it involves every organ system in the body and is critical for maintaining normal body functions, including inflammation. Recent studies have established that in vivo administration of bacterial lipopolysaccharide (LPS) enhances hypothalamic-pituitary-adrenal (HPA) axis function by a mechanism involving endotoxin-stimulated cytokine release.  

IMPORTANCE OF DECREASING INFLAMMATORY ALLOSTATIC LOAD

Deceasing our allostatic load is a component of reaching our optimal health.  Allostatic load refers to the wear and tear on the body through stress. Metabolic endotoxemia contributes to the reduction in our allostatic load. Meeting one’s optimal health includes having a healthy weight, healthy blood sugar levels, and low inflammation among many things. The decreasing allostatic load can be done by increasing physical activity and mindfulness, improving nutrition, reducing stress, maintaining social connections, and getting enough sleep. Decreasing the number of factors involved in the allostatic load will help decrease the overall inflammatory response. 

Don’t know where to start? At the Institute for Human Optimization, we will work with you directly to optimize your well-being. No two patients are the same, so we work with you and create a personalized and individual approach to your health concerns. Contact us today to get started.

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References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695328/

https://diabetes.diabetesjournals.org/content/56/7/1761

https://pubmed.ncbi.nlm.nih.gov/14965237/

https://pubmed.ncbi.nlm.nih.gov/8892362/

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Hashimotos: The Most Common Cause of Hypothyroidism

Hashimoto’s, also known as Hashimoto’s Thyroiditis, is considered to be the most common cause of hypothyroidism. It is an autoimmune disorder that causes your thyroid to produce less than optimal amounts of hormones. The body needs these hormones to regulate its metabolism and other functions. Follow us along as we discuss what Hashimoto’s is and how it relates back to Hypothyroidism.

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Thyroid

The thyroid is a small gland in the front of your neck. It releases hormones that affect everything in the body, from heart rate to energy levels. Hormones produced in the thyroid include T3 and T4, two of the most important thyroid hormones. These hormones are responsible for growth, development, metabolism (the rate at which all chemical processes in the body take place) and many other functions throughout your body.

T3 specifically helps with the thermal regulation of the body and is essential for growth, development, and general homeostasis (stable state).

The thyroid gland produces T4 and then converts it into T3; this conversion process can be inhibited by inflammation. When your body is inflamed (for example, due to injury or illness), your thyroid may not produce enough T3. 

When your thyroid is not working optimally, this can result in an overactive thyroid gland (hyperthyroidism) or an underactive thyroid gland (hypothyroidism).

Thyroid hormones are responsible for many functions throughout the body, including regulating metabolism. It is not rare to see low levels of thyroid and rapid weight gain in the same individual.  Let’s discuss common types of thyroid disorders. 

Hyperthyroidism

Hyperthyroidism is when you have an overactive thyroid gland that generates too much thyroid hormone. This results in symptoms such as:

· Fast heart rate

· Increased appetite

· Excessive perspiration

· Weight loss

· Nervousness, irritability, and/or anxiety

· Diarrhea

· Sensitivity to heat

· And more!

Hypothyroidism

Hypothyroidism is when you have an underactive thyroid gland that does not generate enough thyroid hormone. This results in symptoms such as:

· Fatigue and excessive sleepiness

· Weight gain or inability to lose weight

· Depression, mood swings, and/or irritability

· Muscle pain and stiffness

· Cold intolerance

· Constipation and dry skin

· And more!

Primary, Secondary, Tertiary, and Subclinical Hypothyroidism

There are different types of hypothyroidism. 

  • Primary Hypothyroidism: is when the thyroid gland itself does not maintain adequate levels of T3 or T4. This can be caused by a number of things, but the most common cause in the US is Hashimoto’s Disease. In primary hypothyroidism the problem is with the thyroid itself.
  • Secondary Hypothyroidism: is when the pituitary fails to produce enough Thyroid-Stimulating Hormone (TSH) in response to low levels of thyroid hormone in the blood. This can be caused by pituitary disease, hypothalamic disease, medications that reduce TSH (such as amiodarone or lithium), autoimmune destruction of the pituitary, and more. In secondary hypothyroidism, the issue is not with the thyroid but the  pituitary, which monitors the thyroid.
  • Tertiary Hypothyroidism: is when the hypothalamus fails to produce enough thyrothropin-releasing hormone (TRH).  TRH is needed to stimulate the pituitary to produce enough TSH. TSH is necessary to stimulate the thyroid gland. Research shows that this can be caused by hypothalamic disease, medications that reduce TRH (such as lithium), autoimmune destruction of the hypothalamus, and more.
  • Subclinical hypothyroidism: is an early, mild form of hypothyroidism. Usually, your thyroid is functioning properly but your TSH levels are slightly elevated. This form of hypothyroidism is most common in women, the elderly, and those with other autoimmune diseases.

Hashimoto’s 

The most common cause of hypothyroidism is Hashimoto’s.  It’s important to note that Hashimoto’s and hypothyroidism are not the same conditions. People who have Hashimoto’s often progress to hypothyroidism, or an underactive thyroid.  But not always. Sometimes people can be diagnosed with both at the same time, while some might only ever experience Hashimoto’s and never develop hypothyroidism. Hashimoto’s is an autoimmune disorder. Autoimmune disorders are when your body’s immune system starts attacking healthy cells. In the case of Hashimoto’s, this is when you have an immune system that incorrectly identifies the thyroid gland as something foreign and attacks it, resulting in damage to your thyroid. 

Although Hashimoto’s most often results in hypothyroidism, it can also cause hyperthyroidism, when your thyroid gland is overactive. However, this form of hyperthyroidism may go undetected because some of the symptoms are similar to that of people with Hashimoto’s who present with hypothyroidism (such as weight gain, fatigue, lethargy, lack of concentration).  

What are the symptoms of Hashimoto’s? 

Hashimoto’s is usually asymptomatic for years which makes it difficult to diagnose. One of the first signs of this disease would manifest through fatigue, which is the most common symptom. Other symptoms include weight gain, feeling cold all the time, constipation, and depression.  

With Hashimoto’s, symptoms will worsen as your disease progresses and it becomes harder to recover from them. 

People with Hashimoto’s typically present with:

· A goiter (an enlarged thyroid)

· Decreased TSH levels

Hashimoto’s is caused by antibodies attacking the thyroid, which causes it to not produce enough hormones. The specific triggers for this attack are unknown but there are some ideas on why this happens. Some research links Hashimoto’s to genetics, exposure to viruses and environmental toxins, chronic inflammation, gut health issues, diets high in goitrogens, obesity, soy, and bacterial or viral infections. There is also a belief that Hashimoto’s may be brought on by stress hormones.

Hashimoto’s is important to address because left untreated, it can lead to an underactive thyroid or hypothyroidism. The thyroid gland is responsible for producing thyroxine which is responsible for regulating your metabolism. It also affects the way you use energy, the way your body uses food for energy, how your body molds fat and sugar, as well as how your heartbeats. An underactive thyroid can have long-term health effects such as weight gain, anxiety, lethargy, and depression. 

Personalized Approach to Hashimoto’s

Generally, your health care provider will take your medical history and perform a physical exam. Additionally, they will check your Thyroid Stimulating Hormone (TSH) and your Free T4 (FT4) levels. 

At the Institute for Human Optimization, we believe the best way to help our patients is by having all the insight we can get access to. This in turn helps us create a personalized, precise, protocol unique to you. 

Some blood tests we will look at include but are not limited to:

  • Checking levels of Thyroid peroxidase Ab, Thyroglobulin Ab, and TPO-ab. These are antibodies that are fighting against your thyroid gland.  
  • Total T4 will be reviewed to look into the levels of protein that the thyroid gland produces. 
  • Total T3:   the active form of thyroid hormone 
  • Free T3: the active form of thyroid hormone 
  • Reverse T3: Reverse T3 is a protein that binds to T3. When this happens it makes T3 not available for the body to use, which will make your thyroid gland slow down production of thyroid hormone.
  • Thyroid Binding Globulin: Thyroid Binding Globulin will be tested to look for levels of protein that your thyroid gland produces.  
  • Thyroglobulin Antibodies: the presence of this antibody is a marker for Hashimoto’s disease.

People with Hashimoto’s, or autoimmune hypothyroidism, have special needs when it comes to thyroid hormone replacement therapy.  It can be difficult to find the right type of medication for you – what might work well in one person may not work at all in another patient. 


Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

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Heart Rate Variability

Heart rate variability is a new technique in the field of biofeedback that can help provide a more accurate picture of your physical and emotional state. This blog post will explore what heart rate variability is, how it works, and some benefits you may see from using this new way to track well-being. 

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Heart Rate Variability (HRV) is thought to be originally discovered by K. Grinberg back in 1896 but was not researched until the 1960s. Heart rate variability is a measurement of the time between heartbeats. It can be measured in milliseconds, which are 1/1,000th of a second. HRV is measured by your heart’s response to breathing patterns. As you breathe in, your body absorbs oxygen and nutrients that allow the lungs to release carbon dioxide when you exhale. As the body absorbs oxygen, it sends an electrical signal to the heart muscles to contract. This contraction is what pushes blood throughout your body via the circulatory system. During exhalation, there is less pressure on your heart since no new air comes in with each breath (and you exhale carbon dioxide). A low HRV value means that it takes longer for the heart to relax and fill with blood between beats, causing reduced circulation throughout the body. 

HRV AND SLEEP

Sleep is critical to our overall health.  Not only does our body use this time to repair itself, but it is also an opportunity for the brain to go through stages of mental development. The average adult sleeps 7-8 hours per night. However, not all sleep is created equal. There are 4 stages of sleep and two types of sleep: rapid eye movement (REM) sleep and non-REM sleep (which has three different stages). 

Stage 1: is non-REM sleep. It is described as light sleep and you can be lightly stimulated without waking up. Additionally, your brain waves begin to slow down compared to your daytime activity. 

Stage 2: This stage is a deeper non-REM sleep. It is more difficult to be woken up during this phase, your brain waves further slow down and your body temperature begins to drop.

Stages 3: In these final stages of non-REM sleep, there are very slow brain waves called delta waves.  

Stage 4: REM Sleep. Rem sleep is when your eyes move rapidly back and forth behind your closed eyelids, where you are in a deep sleep but dreaming.

RV is very important when it comes to sleep. In fact, HRV has been successfully used to screen people for possible referral to a Sleep Lab. Typically, an individual’s heart rate will vary the most while awake and then decrease at night during REM sleep.  In non-REM sleep, HRV will begin to decline as your heart rate slows down. In REM sleep, however, HRV begins to pick back up again because it is a very active time for the body and you have a faster heart rate. 

Research has shown that an individual with a low HRV value may have a hard time transitioning from being awake to entering deep REM sleep because their nervous system won’t be able to relax between breaths. This may be one reason why those with a low HRV might have difficulty sleeping or even feel tired during the day. An individual with a high HRV will most likely have an easier time transitioning from wakefulness to sleep, and will also maintain their deep REM sleep throughout the night.

WHY IS HRV IMPORTANT

HRV is important in medicine today. HRV analysis is a recognized tool for the estimation of cardiac autonomic modulations.  Cardiac autonomic modulations refer to the changes of cardiac parasympathetic and sympathetic activity in response to variations in respiratory rates. Heart Rate Variability is the variability within your heart rate over time, which is also measured by taking an ECG recording.  It’s widely used nowadays for tracking health and is even a feature on common smartwatches. HRV has been used to predict mortality after a heart attack, among other things. 

HRV is used as a marker for physical and mental stress. How so? The parasympathetic nervous system lowers heart rate and controls the “rest and digest” function. The sympathetic nervous system raises the heart rate, dilates blood vessels to generate a fight or flight response which is particularly useful when dealing with stressful events. As HRV increases, your cardiac output decreases as you enter a state of parasympathetic dominance. For example, those with depression or Post Traumatic Stress Disorder have been found to have a lower HRV. Low HRV may indicate that the individual has a harder time recovering from daily stressors, which could ultimately lead to health issues if left untreated.

HRV may be able to give some insight into how stress has been affecting your mental and physical health. If an individual is having a hard time maintaining good cognitive function, HRV can be used as a gauge to determine whether that person needs more rest or if they need to take time off from work. In the case of those who have anxiety or depression, low HRV may be able to predict the likelihood of an individual experiencing issues with their mental health.

Generally, a low HRV is linked with an increased risk of death and cardiovascular disease. By taking HRV to heart, individuals are able to get a better picture of their health. There are also times when high HRV may indicate that the person’s body is not operating at its best. An example of this would be an individual who does workouts that are too intense for them to handle. 

INCREASING YOUR HRV

When a person is in a stressful situation, their sympathetic nervous system takes over and an increased amount of cortisol will be released. This leads to a lower HRV which signals the body that there is stress present.

In response, one can attempt to reverse this effect by breathing slowly and deeply while engaging in relaxation techniques such as meditation or yoga. People who have a high HRV have been shown to have higher levels of a neurotransmitter called GABA, which is naturally released when a person is present in a relaxed environment.

Increasing your HRV will also increase the amount of energy that your body uses as it requires less energy from cortisol and adrenaline for this process. This leads to better blood pressure, weight management, performance under stress, and other optimal outcomes.

Just like you may use smart technology to count your steps, tracking HRV may be a useful tool to motivate behavioral and lifestyle change. For example, Sleep HRV measurements can provide insight on how you rate compared to other users in similar age groups. While HRV biometric tracking is still a new concept, I am hopeful it will help patients be more participatory in their health journey. 

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225923/

https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understanding-Sleep

https://pubmed.ncbi.nlm.nih.gov/21658979/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680518/

https://pubmed.ncbi.nlm.nih.gov/27918706/

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